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Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial
- Source :
- Journal of the International AIDS Society
- Publication Year :
- 2020
-
Abstract
- Introduction A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women’s risk of sexually acquiring HIV‐1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use. Methods We measured the amount of dapivirine in returned rings from a placebo‐controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non‐use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time‐dependent covariate for HIV‐1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV‐1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence. Results Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV‐1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV‐1 acquisition estimated 75% to 91% HIV‐1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women
- Subjects :
- Relative risk reduction
Adult
medicine.medical_specialty
Adolescent
Anti-HIV Agents
Sexual Behavior
Dapivirine
HIV prevention
Context (language use)
HIV Infections
Lower risk
Placebo
law.invention
Medication Adherence
03 medical and health sciences
Young Adult
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
medicine
Humans
030212 general & internal medicine
adherence
Research Articles
Randomized Controlled Trials as Topic
clinical trials
030505 public health
business.industry
Public Health, Environmental and Occupational Health
Contraceptive Devices, Female
Middle Aged
Vaginal ring
Confidence interval
Drug Liberation
Infectious Diseases
Pyrimidines
Africa
HIV-1
HIV prevention trials
Female
Pre-Exposure Prophylaxis
women
0305 other medical science
business
Risk Reduction Behavior
Research Article
Subjects
Details
- ISSN :
- 17582652
- Volume :
- 23
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of the International AIDS Society
- Accession number :
- edsair.doi.dedup.....def6657a540b3fc1ce668fc7e6191bfa